Granzyme B mimics apical caspases. Description of a unified pathway for trans-activation of executioner caspase-3 and -7

Granzyme B (GrB) is predicted to trigger apoptosis by activating preferred caspases, but the zymogens that are directly processed by the granzyme and the requirements for these interactions remain unclarified. We examined this dilemma by comparing the kinetics and pattern of GrB-mediated activation of the executioner caspase-7 in vitro and in vivo. GrB rapidly activates procaspase-7 in vitro by cleaving between the large and small subunits leaving the propeptide intact. During GrB-mediated apoptosis, the caspase-7 propeptide is removed and cleavage occurs between the subunits. Strikingly, caspase-7 is unprocessed in caspase-3-deficient MCF-7 cells exposed to GrB but is rapidly activated when the cells are solubilized. Transfection with caspase-3 restores the removal of the caspase-7 propeptide and the capacity of GrB to subsequently activate the caspase. The data suggest that GrB activates caspase-3, which then removes the propeptide of caspase-7 allowing activation by GrB. Thus GrB initiates the death pathway by processing the accessible caspase-3, and the caspase-7 propeptide regulates trans-activation of the zymogen by granzyme. As a consequence, two proteases, caspase-3 and GrB, are required to activate procaspase-7.     

Transverse dimensions of wood pulp fibres by confocal laser scanning microscopy and image analysis

Cross-sectional images of wood-pulp fibres were generated using optical sectioning by a confocal laser scanning microscope. The technique has a distinct advantage over mechanical sectioning with a microtome, as it simplifies specimen preparation. Cross-sectional images were obtained for unbleached softwood kraft pulp fibres using epifluorescence mode. The accuracy of cross-sectional images was verified by imaging fluorescent microspheres. An image analysis procedure, in which the boundaries of fibre cross-sections were defined with a maximum-gradient edge-finding technique, was developed for measuring fibre cross-sectional area and wall thickness rapidly and accurately. The measurements were insensitive to the confocal microscope's asymmetric resolution, signal deterioration through the specimen thickness, overall image quality and operator bias.     

Municipalities and energy efficiency in countries in transition: Review of factors that determine municipal involvement in the markets for energy services and energy efficient equipment,or how to augment the role of municipalities as market players

It is widely recognized that many cost-efficient opportunities to employ end-use energy efficiency measures exist in countries in transition (CITs) and that municipal authorities have an essential role to play in capturing these opportunities. The aim of this paper is to review the factors that determine the degree of involvement of local authorities in the market for energy services and energy efficient (EE) equipment in three CITs: Bulgaria, Hungary and the Former Yugoslav Republic of Macedonia (hereafter: Macedonia). We achieve this aim by examining the current status of local governments as the most powerful determinant of municipal market involvement. Two broad groups of factors are discussed: statutory obligations and powers of local governments, especially energy-related tasks, and finance. We explain how specific features within these two areas may influence the motivation of local authorities to improve energy efficiency and their capacity to do so. We argue that greater decentralization is the first step in augmenting the role of local authorities in the market for energy services and EE equipment. Based on the analysis we give recommendations on how to encourage municipal authorities to use market mechanisms more extensively to deliver energy efficiency.     

Major depression and medication adherence in elderly patients with coronary artery disease.

Little is known about the effects of depression on adherence to medical treatment regimens in older patients with chronic medical illnesses. Poor adherence may explain the increased risk of medical morbidity and mortality found in depressed medical patients. Ten of 55 patients over the age of 64 with coronary artery disease met the criteria for major depression from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987). All patients were prescribed a twice-per-day regimen of low dose aspirin to reduce their risk for myocardial infarction. Medication adherence was assessed for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p?     

Enhancement of solar gains through a roof using a thermal trap

This paper investigates the viability of increasing solar gains through the roof of an air-conditioned room using the thermal trap effect. In solving the heat conduction equations through the thermal trap and the concrete slab, the finite difference method has been employed and the initial conditions are derived from the assumption that, initially, the ceiling of the room and the top of the trap material are in equilibrium with constant room air temperature and the ambient air temperature, respectively. The effect of the thickness of the thermal trap and that of the concrete slab on the thermal flux transferred through the roof have been studied.     

Shock loading of 3D woven composites: A validated finite element investigation

In a companion paper in this issue (Pankow et al., 2010 [1]), experimental results for the deformation response of 3D glass fiber textile composites subjected to shock wave pulse pressure loading were presented. In this paper, finite element models are developed to simulate the deformation response and damage development observed in the experiments. Two levels of models are presented, with the first focused on a layered, homogenous orthotropic model that examined the bulk macroscopic deformation response. In the second model, each layer is represented to capture the interactions between fiber tows and matrix, taking into account the discrete non-homogeneous material distribution in each layer. Both models incorporated a user defined subroutine within the commercial software ABAQUS to capture matrix micro-cracking, which is responsible for damage development and growth. Results from the computational models correlated well with experimental results and observed locations of matrix micro-cracking.     

Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor

The use of a "size-tunable" polyurethane resistive pulse sensor for quantitative sizing of nano- and microparticles is presented. A linear relationship, as first suggested by Maxwell, between particle volume and change in electric resistance across the pore was observed. Particle sizes were quantified for a given size-tunable membrane, by first creating a linear calibration curve to a series of monodisperse carboxylated polystyrene particles of various diameters and then applying this curve to calculate the size of "unknown" nanoparticles. The diameters of a selection of synthetic and biological particles, being PMMA and nonfunctionalized polystyrene particles, along with biological nanoparticles (adenovirus) were calculated using this methodology. Calculated particle diameters and coefficients of variation were shown to be in good agreement with both transmission electron microscopy and dynamic light scattering results.